Main Session
Oct
01
QP 19 - GI 4: Quick Pitch: Enhancing Efficacy for Esophageal Cancer and Radiation Responders for Rectal Cancer
1111 - Peripheral Blood Immune Cell Dynamics as Indicators and Predictors of Clinical Response to Immunotherapy Based Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer
Presenter(s)
Yaqi Wang, MD - Fudan University Shanghai Cancer Center, Shanghai, Shanghai
Y. Lin1,2, Y. Wang1,2, F. Xia1,2, L. Shen1,2, J. Wan1,2, H. Zhang1,2, Y. Wang1,2, R. Wu1,2, S. Cai1,3, Y. Xu1,3, and Z. Zhang1,2; 1Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China, 2Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, 3Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
Purpose/Objective(s):
The integration of PD-1 inhibitors with total neoadjuvant therapy (TNT) has achieved remarkable tumor regression in patients with locally advanced rectal cancer (LARC) in our previous TORCH trial. It's important to explore appropriate biomarkers to predict the efficacy and probably help the decision making after iTNT (surgery or watch and wait). Herein, we investigate the relationship between the serial assessments of peripheral blood cell counts and cytokine levels and the efficacy of iTNT.Materials/Methods:
We retrospectively collected data from patients with locally advanced rectal cancer treated with short-course radiotherapy and 6 cycles of CAPOX and PD-1 inhibitor from TORCH trial (NCT04518280). Demographics, disease characteristics, and laboratory data, including leukocytes by complete blood cell count, lymphocyte subsets using flow cytometry and serum levels of twelve cytokines were described before, during, and after iTNT. The variation (?) of each marker was calculated as POST minus PRE value of individual patients. The clinical outcome complete response (CR) was defined as pathological complete response after surgery plus cCR patients who accepted watch-and-wait. The continuous data of patients in the CR and non-CR groups were compared using Student’s t test and the non-parametric Mann–Whitney U-test. Univariate and multivariate logistic regression analyses were used to determine the factors predicting the treatment responses of patients.Results:
A total of 95 patients were included. In baseline samples, differential analysis revealed that absolute counts of CD3+CD8+T cells was significantly higher in patients in the non-CR group (median 434.00 vs. 289.50, p=0.01); however, the counts of other lymphocyte subsets, white blood cell subsets, and the 12 cytokines showed no significant differences between CR and non-CR group. After iTNT, higher proportion of CD4+CD25+CD127 low/- T cells was observed in patients in CR group (median 7.75 vs. 13.05, p=0.04). In terms of the variation, ?CD3-CD19+ B cells (median -2.26 vs. -1.83, p=0.03), ?CD3+CD8+ T cells (median -122.00 vs. -7.00, p=0.03) and ?CD3+CD4+ T cells (median -188.00 vs. -98.00, p=0.04) revealed a significant decrease in non-CR group compared to CR group. In contrast, ?EOS proportion was significantly higher in the CR group (median 0.03 vs. 0.11, p=0.03). After adjusted for the above features and other baseline characteristics, multivariate logistic regression analyses showed that ?absolute CD3-CD19+B cells is still an independent predictor (OR: 1.015(1.002-1.033), p=0.05).Conclusion:
Serial peripheral blood immune cell monitoring could be used to predict tumor response of LARC patients with iTNT. The variation in absolute CD3-CD19+ B cells was significantly lower in the CR group and was identified as an independent predictor of CR, suggesting it may be a promising peripheral-blood marker for predicting tumor response.